What are non-benzodiazepine (non-BZD) anti-anxiolytic (anxiety-reducing) medications with immediate onset of action?

From the Guidelines

Non-benzodiazepine anti-anxiety medications with immediate effects include melatonin, gabapentinoids, and certain antihistamines, with melatonin being a preferred option due to its effectiveness and few side effects, as reported in a high-grade quality of evidence meta-analysis 1. When considering non-benzodiazepine anti-anxiety medications, it's essential to prioritize those with immediate onset of action, especially in situations where benzodiazepines are contraindicated.

• Melatonin, administered as tablets or sublingually, has been shown to provide effective preoperative anxiolysis with few side effects compared to placebo, and its effectiveness is comparable to midazolam 1.
• Gabapentinoids, such as gabapentin and pregabalin, are increasingly used as oral pre-anaesthetic medications for their opioid-sparing effects, but their use should be limited to a single and lowest preoperative dose due to potential adverse effects, including sedation, dizziness, and visual disturbances 1.
• Buspirone, typically starting at 5-7.5 mg twice daily, may take 1-2 weeks for full effect, despite some patients reporting earlier relief, and is not considered to have an immediate onset of action 1.
• Hydroxyzine can be prescribed at 25-50 mg four times daily for immediate anxiety relief, working within 30-60 minutes, but its use should be cautious due to potential side effects, such as sedation and dry mouth.
• Beta-blockers like propranolol (10-40 mg as needed) can quickly reduce physical symptoms of anxiety, such as trembling and palpitations, but are not considered a primary treatment for anxiety. It's crucial to consider the potential risks and benefits of each medication, as well as individual patient factors, such as substance use disorders or respiratory conditions, when selecting a non-benzodiazepine anti-anxiety medication. Non-pharmacological approaches, like deep breathing, progressive muscle relaxation, and grounding techniques, should be used alongside medication for optimal results.

From the FDA Drug Label

The mechanism of action of buspirone is unknown. Buspirone differs from typical benzodiazepine anxiolytics in that it does not exert anticonvulsant or muscle relaxant effects. It also lacks the prominent sedative effect that is associated with more typical anxiolytics. Peak plasma levels of 1 ng/mL to 6 ng/mL have been observed 40 to 90 minutes after single oral doses of 20 mg.

Non-benzodiazepine (non-BZD) anti-anxiolytic medications with immediate onset of action are not explicitly described in the provided text, but buspirone is a non-BZD anti-anxiolytic with a rapid absorption and peak plasma levels reached within 40 to 90 minutes after oral administration.

• Buspirone may be considered as a non-BZD anti-anxiolytic medication, but its onset of action may not be immediate, as peak plasma levels are reached within 40 to 90 minutes. 2

From the Research

Non-Benzodiazepine Anti-Anxiolytic Medications

• Non-benzodiazepine anxiolytics can be divided into several categories, including those that are not primarily used as anxiolytics, those that pharmacologically but not chemically resemble benzodiazepines, and those that are novel both chemically and pharmacologically 3
• Examples of non-benzodiazepine anxiolytics include:
  • Antidepressants
  • Antipsychotic drugs
  • Antihistamines (such as hydroxyzine) 4, 5
  • Beta-adrenergic antagonists
  • Buspirone, which seems to act on 5-HT mechanisms 3, 6
  • Alpidem and zuriclone, which act on the benzodiazepine/GABA complex 3

Immediate Onset of Action

• Buspirone has been noted to have a 'lagtime' of 1 to 2 weeks to the onset of anxiolytic effect, and may not be considered to have an immediate onset of action 6
• Hydroxyzine, an antihistamine, has been shown to be effective in alleviating the acute symptoms of generalized anxiety disorder (GAD), but its onset of action is not explicitly stated as immediate 4
• There is a need for the development of new anxiolytic drugs that are fast-acting and free from the unwanted effects associated with traditional benzodiazepines, such as tolerance or dependence 5

Pharmacological Properties

• Buspirone lacks hypnotic, anticonvulsant, and muscle relaxant properties, and has been termed 'anxioselective' 6
• Buspirone is effective in patients with mixed anxiety/depression, and has a low incidence of sedation compared to benzodiazepines 6
• Hydroxyzine has been associated with a higher rate of sleepiness/drowsiness compared to other anxiolytic agents 4